Institut Pasteur, Unité de Régulation Immunitaire et Vaccinologie, Département d'Immunologie, Paris, France.
Blood. 2012 Jul 5;120(1):90-9. doi: 10.1182/blood-2012-02-410936. Epub 2012 May 18.
The physiologic role played by plasmacytoid dendritic cells (pDCs) in the induction of innate responses and inflammation in response to pathogen signaling is not well understood. Here, we describe a new mouse model lacking pDCs and establish that pDCs are essential for the in vivo induction of NK-cell activity in response to Toll-like receptor 9 (TLR9) triggering. Furthermore, we provide the first evidence that pDCs are critical for the systemic production of a wide variety of chemokines in response to TLR9 activation. Consequently, we observed a profound alteration in monocyte, macrophage, neutrophil, and NK-cell recruitment at the site of inflammation in the absence of pDCs in response to CpG-Dotap and stimulation by microbial pathogens, such as Leishmania major, Escherichia coli, and Mycobacterium bovis. This study, which is based on the development of a constitutively pDC-deficient mouse model, highlights the pivotal role played by pDCs in the induction of innate immune responses and inflammation after TLR9 triggering.
浆细胞样树突状细胞 (pDCs) 在病原体信号诱导固有免疫反应和炎症中的生理作用尚不清楚。在这里，我们描述了一种缺乏 pDCs 的新型小鼠模型，并证实 pDCs 对于 TLR9 触发后体内 NK 细胞活性的诱导是必需的。此外，我们提供了第一个证据，表明 pDCs 对于 TLR9 激活后系统性产生多种趋化因子至关重要。因此，我们观察到在缺乏 pDCs 的情况下，CpG-Dotap 和微生物病原体（如利什曼原虫、大肠杆菌和牛分枝杆菌）刺激后，炎症部位单核细胞、巨噬细胞、中性粒细胞和 NK 细胞的募集发生了深刻的改变。这项基于构建一种组成性 pDC 缺陷小鼠模型的研究强调了 pDCs 在 TLR9 触发后诱导固有免疫反应和炎症中的关键作用。
